The proposed studies are designed to identify the structural characteristics or defects which account for the functional behavior of two abnormal fibrinogens and of human fetal fibrinogen. Functional characterization will be pursued by analysing the rates of fibrinopeptides A and B release, of fibrin aggregation, the crosslinking behavior, capacity to interact with fibrinectin and to support platelet aggregation, the effect (if any) of the abnormal on the function of normal fibrinogen, and fibrinogen heterogeneity in plasma. Structural analyses will include carbohydrate content, chromatographic (DEAE-c) electrophoretic, and isoelectric behavior of both intact fibrinogen and of circulating catabolites. Isolated S-carboxymethyl chains which are identifiable as abnormal will be subjected to cyanogen bromide and/or to tryptic digestion in order to identify abnormal peptides by peptide maps, electrophoretic, or chromatographic means. Plasmic derivatives will be obtained and their polypeptide chains will be isolated in an effort to identify the segments of the chain which bear the abnormality. Analyses of the abnormal peptides will include amino acid content and sequence, and carbohydrate content. Plasma from available family members will be examined to assess the hereditary nature of each fibrinogen abnormality. It is hoped that these studies will provide useful insights relating to the functional domains or regions of fibrinogen, and to the post- or pre-transcriptional nature of fetal fibrinogen and of the abnormal fibrinogens identified in this proposal.